Terminal differentiation of mammalian epidermal keratinocytes eventually creates a keratin filament matrix encased within a sheet of covalently cross-linked proteins called the cornified cell envelope (CE). Biogenesis of the CE is being studied in both normal and diseased states, e.g. psoriasis. STEM measurements of mass/area on purified CEs allow one to evaluate their homogeneity and test for possible specialized areas within a given CE. CEs isolated from human epidermis (normal and psoriatic), mouse epidermis (normal and transgenic), other epithelia, and cultured keratinocytes are being studied.